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Effects of protein kinase and phosphatase inhibitors on bioelectric responses of guinea-pig tracheal epithelium to hyperosmolarity and methacholine (MCh).
Jing Y; Van Scott MR; Fedan JS
FASEB J 2005 Mar; 19(5)(Pt 2):A1549
Release of epithelium-derived relaxing factor (EpDRF) is linked to epithelial ion transport, but the mechanistic relationship is unclear. Thus, an apparatus was developed to allow measurement of transepithelial potential differnece (Vt), resistance (Rt), and diameter of perfused trachea. Extraluminal MCh (0.3 :M) contracted, whereas intraluminal (IL) D-mannitol (D-M, 30 mosM) relaxed the tracheas. Both MCh and D-M increased Vt but had no effect on Rt. The PKC inhibitor, chelerythrine (20 :M, IL), decreased basal Vt and inhibited MCh-and D-M-induced hyperpolarization without affect Rt. The JNK inhibitors, SP 600125 (30 :M, IL) and dicumarol (15 :M, IL), potentiated MCh-induced hyperpolarization, but no change in Rt was observed. In contrast, the JNK inhibitors inhibited D-M-induced hyperpolarization, and D-M increased Rt in the presence of the JNK inhibitors. NaAsO2 (300 :M, IL) decreased basal Vt, did not affect MCh responses, but mimicked the effect of the JNK inhibitors on the response to D-M. The phosphatase inhibitor, Na3VO4 (300 :M, IL), increased basal Vt and inhibited MCh- and D-M-induced hyperpolarization; MCh decreased Rt in the presence of Na3VO4. The results suggest that basal Vt is regulated by kinases, and that bioelectric responses that accompany contraction/relaxation responses to MCh and hyperosmolarity may be distinguished by their senstivity to JNK inhibitors.
Proteins; Bioelectric-effects; Laboratory-animals; Animals; Animal-studies; Sensitivity-testing; Ion-transport
Abstract; Conference/Symposia Proceedings
Issue of Publication
The FASEB Journal
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